Two Subtypes of Mucinous Adenocarcinoma of The Colorectum: Clinicopathological and Genetic Features Sarli Leopoldo, MD, 1 Bottarelli Lorena, BScD, 2 Azzoni Cinzia, BScD, 2 Di Cola Gabriella, BScD, PhD, 3 Barilli Angela Luciana, MathD, 4 Costi Renato, MD, PhD, 1 Mazzeo Antonio, MD, 1 Salvemini Carlo, MD, 1 Porrini Cristina, MD, 1 Cecchini Stefano, MD, 1 Taglia Maurizio, MD, 1 Roncoroni Luigi, MD, 1 and Bordi Cesare, MD 2 1 Department of Surgical Sciences, Section of General Surgical Clinics and Surgical Therapy, Parma University, Medical School, Parma, Italy 2 Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, Parma University, Medical School, Parma, Italy 3 Research Laboratory ‘‘Biotech’’, Parma, Italy 4 Department of Internal Medicine and Biomedical Sciences, Parma University, Parma, Italy Background: This work is aimed at comparing mucinous colorectal adenocarcinomas (MUC) and non-mucinous colorectal adenocarcinomas (non-MUC), and at verifying the existence of two different subgroups of MUC, in terms of clinicopathological features, chromosomal alterations, and outcome, in a geographical area where mucinous colorectal cancer resulted as being very frequent. Methods: One hundred and fifty-six unselected patients who underwent curative colorectal resection for sporadic colorectal cancer over a 4-year period were evaluated for histological classification as to MUC and non-MUC subtype, for microsatellite instability (MSI) using six microsatellite markers, and for the presence of p27, Fhit, and cyclooxygenase-2 (Cox-2). Molecular data, immunohistochemical results, recurrence frequency, and patient survival were analyzed statistically in relation to histological subtypes. Results: MUC accounted for 38.5% of all colorectal carcinomas. Compared to non-MUCs, MUCs were more frequently located in the proximal colon (p < 0.001), and more frequently showed MSI phenotype (p < 0.001), altered protein expression of hMlh1 (p = 0.030), Fhit (p <0.001), and p27 (p < 0.001). Compared to MUC with microsatellite-stable (MSS) pheno- type, MUC with MSI more frequently resulted as being located in the proximal colon (p = 0.013), and more frequently showed altered expression of hMlh1 (p < 0.001), hMsh2 (p = 0.008), Fhit (p < 0.001), and p27 (p = 0.015). Significantly better survival of patients with proximal MUC (p = 0,012), with MSI MUC (p = 0.017), and with MUC with altered p27 expression (p = 0.02). Conclusion: The results of the present study confirm that MUC represents distinct clini- copathological and genetic features as compared to non-mucinous tumors and support the hypothesis that MUC includes two subtypes with different genetic pathways and behavior. Mucinous adenocarcinoma, one of the histological subtypes of colorectal cancer (CRC), is defined as a tumor with >50% of its body showing a mucinous pattern on histological examination, and with a large amount of extracellular mucin produced by secreting acini. 1 This is distinct from signet-ring adenocarci- Published online February 27, 2008. This work was supported in part by a grant from ‘‘Lega Italiana per la lotta contro i tumori’’ Address correspondence and reprint requests to: Sarli Leopoldo, MD; E-mail: leosarli@unipr.it Publishedby Springer Science+Business Media, LLC Ó 2008 The Society of Surgical Oncology, Inc. Annals of Surgical Oncology 15(5):1429–1439 DOI: 10.1245/s10434-007-9757-1 1429